Development of a Prediction Model for Short-Term Remission of Patients with Crohn's Disease Treated with Anti-TNF Drugs.

Therapy with anti-tumor necrosis factor (TNF) has dramatically changed the natural history of Crohn's disease (CD). However, these drugs are not without adverse events, and up to 40% of patients could lose efficacy in the long term. We aimed to identify reliable markers of response to anti-TNF drugs in patients with CD. A consecutive cohort of 113 anti-TNF naive patients with CD was stratified according to clinical response as short-term remission (STR) or non-STR (NSTR) at 12 weeks of treatment. We compared the protein expression profiles of plasma samples in a subset of patients from both groups prior to anti-TNF therapy by SWATH proteomics. We identified 18 differentially expressed proteins (p ≤ 0.01, fold change ≥ 2.4) involved in the organization of the cytoskeleton and cell junction, hemostasis/platelet function, carbohydrate metabolism, and immune response as candidate biomarkers of STR. Among them, vinculin was one of the most deregulated proteins (p < 0.001), whose differential expression was confirmed by ELISA (p = 0.054). In the multivariate analysis, plasma vinculin levels along with basal CD Activity Index, corticosteroids induction, and bowel resection were factors predicting NSTR.

Prevalence of iron deficiency without anaemia in inflammatory bowel disease and impact on health-related quality of life. / Prevalencia de déficit de hierro sin anemia en la enfermedad inflamatoria intestinal y su impacto en la calidad de vida.

INTRODUCTION: Iron deficiency without anaemia (IDWA) is commonly found in outpatients with inflammatory bowel disease (IBD) in an even higher proportion than anaemia. However, its true prevalence and possible impact on health-related quality of life (HRQoL) are unknown. The objectives of this study were: to establish the prevalence of IDWA, identify possible associated factors and measure their impact on HRQoL. MATERIAL AND METHODS: 127 patients with IBD in an outpatient setting were consecutively included in an observational, descriptive, cross-sectional study. IDWA was defined as ferritin levels of <100 ng/ml with inflammatory activity or ≤30 ng/ml without it, with transferrin saturation of ≤16%, and with normal haemoglobin levels. HRQoL was assessed using two questionnaires: the IBDQ-9 for symptoms related to IBD and the FACIT-F to measure the presence of fatigue. Fatigue was considered extreme with a score of ≤30 points. RESULTS: The prevalence of IDWA was 37%. Variables associated with its occurrence were female gender (OR=2.9; p=.015) and the presence of inflammatory activity (OR=9.4; p=.001). Patients with IDWA presented HRQoL questionnaires with lower overall scores; decreases of 6.6 (p<.001) and 4.3 (p=.037) points in the IBDQ-9 and the FACIT-F were recorded, respectively. In addition, an increase of 29.4% in the presence of extreme fatigue was observed. CONCLUSION: The prevalence of IDWA is considerable in outpatients with IBD. IDWA is associated with female gender and inflammatory activity. It has a clear negative impact on HRQoL. A more active approach is needed to treat this complication.

Evolution after switching to biosimilar infliximab in inflammatory bowel disease patients in clinical remission. / Evolución tras el intercambio a infliximab biosimilar en pacientes con enfermedad inflamatoria intestinal en remisión clínica.

BACKGROUND AND AIM: The biosimilar of infliximab (CT-P13) has been approved for the same indications held by the infliximab reference product (Remicade®); however, there are few clinical data on switching in inflammatory bowel disease (IBD). The aim of this study was to assess the efficacy, safety, bioavailability profile and factors associated with relapse after switching to biosimilar infliximab in IBD patients in clinical remission. MATERIAL AND METHOD: Observational study with IBD patients treated with Remicade® for at least 6 months and in clinical remission for at least 3 months who switched to infliximab biosimilar. The incidence of relapse, adverse effects and possible changes in drug bioavailability (trough level and antidrug antibodies) were evaluated. RESULTS: Thirty six patients were included (63.9% CD) with a mean follow-up of 8.4 months (SD±3.5). The 13.9% had clinical relapse. The longer clinical remission time before switching (HR=0.54, 95% CI=0.29-0.98, P=.04) and detectable infliximab levels at the time of switching (HR=0.03, 95% CI=0.001-0.89, P=.04) were associated with a lower risk of relapse. No differences were found between infliximab levels at the time of switching and at weeks 8 and 16 (P=.94); 8.3% of the patients had some adverse event, requiring the suspension of biosimilar in one patient for severe pneumonia. CONCLUSION: Switching to biosimilar infliximab in a real-life cohort of IBD patients in clinical remission did not have a significant impact on short-term clinical outcomes. The factors associated with relapse were similar to those expected in patients continuing with Remicade®.

Adherence to a predefined vaccination program in patients with inflammatory bowel disease.

INTRODUCTION: The application of vaccination programs in patients with inflammatory bowel disease (IBD) is heterogeneous and generally deficient. As a result, adherence in these patients to a predefined vaccination program has not been clearly established. The aim of this study was to estimate adherence to a predefined vaccination program among patients with IBD and to identify the factors that may predict poor adherence. METHODS: All patients diagnosed with IBD and followed-up between January and March 2012 were referred to the Department of Preventive Medicine for evaluation of their immune status (with serological testing for hepatitis A, B and C viruses, varicella-zoster virus, mumps, rubella and measles), followed by vaccination based on the test results obtained and on the patient's vaccination history. The percentage of adherence to the vaccination program was determined, along with the factors associated with low adherence. RESULTS: A total of 153 patients with IBD (ulcerative colitis in 50.3% and Crohn's disease in 49.7%) were included (45.1% men and 54.9% women; mean age 43.30±14.19 years, range 17-83). The vaccination program adherence rate was 84.3%. The factors associated with poor adherence were drugs related to IBD (patients not receiving immunosuppressants and/or biological agents showed lower adherence than those receiving these treatments; p=0.021), adherence to medical treatment (poor adherence to treatment was also associated with poor adherence to vaccination; p=0.016), and marital status (single, divorced or separated patients showed lower adherence than married individuals; p=0.015). CONCLUSION: Adherence to vaccination is acceptable among patients with IBD. However, specific actions, such as optimization of patient information on the disease and emphasis on the need for adequate vaccination, are to improve adherence.

Evolución tras el intercambio a infliximab biosimilar en pacientes con enfermedad inflamatoria intestinal en remisión clínica / Evolution after switching to biosimilar infliximab in inflammatory bowel disease patients in clinical remission

Introducción y objetivo: Infliximab biosimilar (CT-P13) ha sido aprobado para las mismas indicaciones que infliximab original (Remicade(R)); sin embargo, hay pocos datos clínicos sobre el intercambio en la enfermedad inflamatoria intestinal (EII). El objetivo del estudio fue evaluar la eficacia, la seguridad, el perfil de biodisponibilidad y los factores asociados a la recidiva tras el intercambio a infliximab biosimilar en pacientes con EII en remisión clínica. Material y métodos: Estudio observacional con pacientes con EII tratados con Remicade(R) durante al menos 6 meses y en remisión clínica durante al menos 3 meses, a los que se realizó el intercambio a infliximab biosimilar. Se evaluó la incidencia de recidiva, los efectos adversos y los cambios en la biodisponibilidad del fármaco (niveles y anticuerpos). Resultados: Se incluyeron 36 pacientes (63,9% EC), con una media de seguimiento de 8,4 meses (±3,5). El 13,9% presentaron recidiva clínica. El mayor tiempo de remisión clínica previo al intercambio (HR=0,54; IC 95%=0,29-0,98; p=0,04) y niveles de infliximab detectables en el momento del intercambio (HR=0,03; IC 95%=0,001-0,89; p=0,04) se asociaron a menor riesgo de recidiva. No hubo diferencias entre niveles de infliximab en el momento del intercambio y en las semanas 8 y 16 (p=0,94). El 8,3% presentaron algún efecto adverso, requiriendo suspensión del fármaco en un paciente por neumonía grave. Conclusión: El intercambio a infliximab biosimilar en una cohorte de vida real de pacientes con EII en remisión clínica no parece tener un impacto significativo en los resultados clínicos a corto plazo. Los factores asociados con la recidiva fueron similares a los esperados en pacientes que continúan con Remicade(R) (AU)

Background and aim: The biosimilar of infliximab (CT-P13) has been approved for the same indications held by the infliximab reference product (Remicade(R)); however, there are few clinical data on switching in inflammatory bowel disease (IBD). The aim of this study was to assess the efficacy, safety, bioavailability profile and factors associated with relapse after switching to biosimilar infliximab in IBD patients in clinical remission. Material and method: Observational study with IBD patients treated with Remicade(R) for at least 6 months and in clinical remission for at least 3 months who switched to infliximab biosimilar. The incidence of relapse, adverse effects and possible changes in drug bioavailability (trough level and antidrug antibodies) were evaluated. Results: Thirty six patients were included (63.9% CD) with a mean follow-up of 8.4 months (SD±3.5). The 13.9% had clinical relapse. The longer clinical remission time before switching (HR=0.54, 95% CI=0.29-0.98, P=.04) and detectable infliximab levels at the time of switching (HR=0.03, 95% CI=0.001-0.89, P=.04) were associated with a lower risk of relapse. No differences were found between infliximab levels at the time of switching and at weeks 8 and 16 (P=.94); 8.3% of the patients had some adverse event, requiring the suspension of biosimilar in one patient for severe pneumonia. Conclusion: Switching to biosimilar infliximab in a real-life cohort of IBD patients in clinical remission did not have a significant impact on short-term clinical outcomes. The factors associated with relapse were similar to those expected in patients continuing with Remicade(R) (AU)

Adherence to a predefined vaccination program in patients with inflammatory bowel disease / La adhesión a un programa de vacunación predefinido en pacientes con enfermedad inflamatoria intestinal

INTRODUCTION: The application of vaccination programs in patients with inflammatory bowel disease (IBD) is heterogeneous and generally deficient. As a result, adherence in these patients to a predefined vaccination program has not been clearly established. The aim of this study was to estimate adherence to a predefined vaccination program among patients with IBD and to identify the factors that may predict poor adherence. METHODS: All patients diagnosed with IBD and followed-up between January and March 2012 were referred to the Department of Preventive Medicine for evaluation of their immune status (with serological testing for hepatitis A, B and C viruses, varicella-zoster virus, mumps, rubella and measles), followed by vaccination based on the test results obtained and on the patient's vaccination history. The percentage of adherence to the vaccination program was determined, along with the factors associated with low adherence. RESULTS: A total of 153 patients with IBD (ulcerative colitis in 50.3% and Crohn's disease in 49.7%) were included (45.1% men and 54.9% women; mean age 43.30 ± 14.19 years, range 17-83). The vaccination program adherence rate was 84.3%. The factors associated with poor adherence were drugs related to IBD (patients not receiving immunosuppressants and/or biological agents showed lower adherence than those receiving these treatments; p = 0.021), adherence to medical treatment (poor adherence to treatment was also associated with poor adherence to vaccination; p = 0.016), and marital status (single, divorced or separated patients showed lower adherence than married individuals; p = 0.015). CONCLUSION: Adherence to vaccination is acceptable among patients with IBD. However, specific actions, such as optimization of patient information on the disease and emphasis on the need for adequate vaccination, are to improve adherence

INTRODUCCIÓN: La implantación de programas de vacunación en pacientes con enfermedad inflamatoria intestinal (EII) es heterogénea y en general, deficiente, por lo que no es bien conocida la adherencia de nuestros pacientes con EII a un programa de vacunación previamente establecido. El objetivo fue determinar la adherencia a un programa de vacunación establecido en nuestro centro en pacientes con diagnóstico de EII y definir qué factores pueden predecir una baja adherencia a dicho programa. MATERIAL Y MÉTODOS: Se derivaron al Servicio de Medicina Preventiva todos los pacientes con diagnóstico de EII revisados en consulta entre enero y marzo de 2012, con el fin de determinar su estado de inmunización (mediante la extracción de analítica con serologías del virus de la hepatitis A, B y C, virus varicela-zoster, parotiditis, rubeola y sarampión) y, posteriormente, ser vacunados teniendo en cuenta sus resultados así como el calendario vacunal previo. Se determinó el porcentaje de adherencia a dicho programa así como los factores relacionados con una baja adherencia. RESULTADOS: Se incluyeron 153 pacientes (45.1% hombres y 54.9% mujeres, con una edad media de 43.30±14.19 años, rango 17-83) con diagnóstico de EII (50.3% colitis ulcerosa y 49.7% enfermedad de Crohn). La adherencia al programa de vacunación fue del 84.3%. Los factores que se asociaron con una baja adherencia fueron: fármacos en relación con la EII (los pacientes que no tomaban inmunosupresores y/o biológicos presentaron una menor adherencia frente aquellos que sí los recibían, p 0.021), adherencia al tratamiento médico (aquellos con mala adherencia al tratamiento presentaron también baja adherencia a la vacunación, p 0.016), estado civil (solteros, divorciados o separados presentaron menor adherencia respecto a los casados, p 0.015). CONCLUSIÓN: La adherencia a la vacunación no es adecuada en pacientes con EII. Acciones específicas como la optimización de la información que se le proporciona al paciente acerca de su enfermedad y la necesidad de una adecuada vacunación, constituye un pilar fundamental para lograr mejorarla